In patients with chronic kidney disease not on dialysis, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) slow the progression of diabetic nephropathy and reduce cardiovascular (CV) risk. However, data on their effectiveness in patients undergoing peritoneal dialysis (PD) are limited. Objectives: The objective of this observational study is to assess the relationship among ACEI or ARB use, preservation of residual renal function (RRF), and CV outcomes and death (cause specific and all-cause) in patients initiating PD. We will further explore any potential inter-clas differences in the association between ACEI vs. ARB use and these outcomes. Our first aim is to assess potential correlates of ACEI or ARB use. Candidate factors include demographic characteristics, concurrent co-morbid conditions, dialysis characteristics, and provider factors. Our second aim is to define the association between ACEI or ARB use and preservation of RRF, which will be calculated as the average of the 24 hour creatinine and urea clearances. We hypothesize that ACEI or ARB use will be associated with better preservation of RRF. We will also examine whether known determinants of loss of RRF modify this association. Our third aim is to evaluate the associations among ACEI or ARB use and the risk of CV outcomes, including myocardial infarction, hospitalization for heart failure, and cardiac cause of death, and all-cause mortality. We hypothesize that use of ACEI or ARB will be associated with lower rates of these outcomes. We will additionally study whether RRF (any vs. none) modifies these associations. Methods: We will use 2 data sources: A) electronic medical records of DaVita, Inc., will contain update medication lists as well as detailed information on vital signs and laboratory measurements; B) the U.S. Renal Data System. The first aim will employ modified multivariable Poisson regression to test for any cross-sectional associations at 90 days after dialysis initiatio between ACEI or ARB use and numerous candidate characteristics. For our second and third aims, we will use multivariable time-to-event analyses to assess the associations between ACEI or ARB use and the clinical events of interest. We will further employ advanced statistical methods, including propensity score techniques; marginal structural models; instrumental variable analyses; repeated measures regression; missing data analysis and imputation; and competing risk models. Significance: Our research will capitalize on an unusually large and detailed dataset of patients initiating PD. In light of limited evidence supporting the use of ACEI or ARB in patients undergoing PD, additional studies are sorely needed, especially based on cohorts of typical patients in usual care settings. Further, the size of the database will allow us to study relevant patient subgroups. PUBLIC HEALTH RELEVANCE: Peritoneal dialysis is a life-saving treatment for many Americans with life-threatening end-stage renal disease. Results of our research may lead to routine use of a class of medication that has the potential to improve their health.